Background: Musculoskeletal (MSK) discomfort is a significant occupational hazard for eye care professionals, including ophthalmologists, who report high rates of MSK discomfort. This systematic review investigated the impact of various interventions, such as regular exercise, posture-correcting aids, and surgical heads-up displays, on reducing MSK pain in the operating room. Methods: This review was reported following PRISMA guidelines and was prospectively registered in the PROSPERO database (CRD42024559189). A systematic literature search was conducted of Embase, MEDLINE, and Web of Science from inception to 2024. Included studies were categorized as exercise modifications, equipment modifications, or training aids. All MSK pain-related outcomes from any time point were extracted. Risk of bias was assessed using the Murad tool, the Cochrane risk-of-bias tool for randomized trials (RoB 2), and the Risk Of Bias In Non-Randomized Studies-of Interventions (ROBINS-I) tool. Results: The systematic search strategy identified 2276 studies, of which 53 qualified for full-text screening with 13 resultant studies including 712 eyecare specialists. Physical activity was found unanimously to reduce MSK pain, with favourable evidence for the utilization of posture-correcting aids. There was mixed—but mostly favourable—evidence for the use of surgical heads-up displays. Conclusions: Exercise modifications, such as yoga and regular exercise; equipment modification with heads-up displays during surgery; and training aids for posture correction were shown to be beneficial for MSK-related pain among ophthalmologists. Future studies should strive to improve the certainty of evidence on ergonomics-related interventions for ophthalmologists, which will better support practice and guideline development.